The objective of the proposed research is to characterize inherited growth disorders caused by specific gene mutations in the mouse and exploit these genetic tools to further our understanding of both normal and abnormal growth processes in mammals. The research will concentrate on two established and one new mutation that are animal models of ateliotic dwarfism (in man, Isolated-Growth-Hormone-Deficiency and Familial-Panhypopituitarism) and two new mutations that result in disproportionate-dwarfism. Mouse models of ateliotic dwarfism will be investigated by approaches in vivo and in vitro to determine whether the site of mutated gene action resides in the pituitary or hypothalamus. Methods include hormone analyses by radioimmunoassay, transplantation of pituitaries, specific antibody localization and ultrastructural analyses of hormone producing cell types in pituitaries, live animal measures, hypothalamic extraction for growth hormone releasing activity, and experiments on hormone synthesis, storage and release from pituitaries cultured in vitro. Mouse models of disproportionate dwarfism will be investigated by growth studies, organ and skeletal measurements, parabiosis, organ grafts, plasma hormone and metabolite measurements and, for each mutant, determination of effective symptomatic and prophylactic treatment.